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Ecstasy affects memory through serotonin

A team of researchers at the Hopkins School of Medicine have uncovered new details about the chemistry of memory performance. They did this in an interesting way: by studying the brains of ecstasy users who frequently report memory problems.

3,4-methylenedioxymethamphetamine (MDMA), more commonly known by its street name "ecstasy," is a recreational drug taken widely in club and party settings. Prized for inducing feelings of euphoria, the drug is sometimes taken in multiple doses over the course of a night.

Beyond being used for recreation, however, the drug is also recognized as a serotonergic neurotoxin, meaning it has adverse effects on the class of neurons that use the neurotransmitter serotonin. Until this study was conducted, however, it remained unclear as to whether or not MDMA was injurious to dopaminergic neurons within the brain as well.

"In the case of MDMA, studies on animals have shown that damage is generally directed towards brain serotonin neurons unless given at high doses or high temperatures," principal investigator Una McCann said.

"Our recently published study was intended to determine whether people who 'binged' on MDMA, like animals given high dosages of MDMA, developed dopamine neurotoxicity in addition to serotonin neurotoxicity," McCann said.

"We also hoped to determine whether loss of brain serotonin markers, as measured using positron emission tomography (PET) was related to memory problems that have previously been found in abstinent MDMA users." For the purposes of the study, abstinent users are those who had not taken the drug for at least two weeks prior to the study.

In order to test these hypotheses, 16 abstinent MDMA users and 16 control subjects were examined using positron emission topography. PET is an advanced neuroimaging technique that measures cerebral blood flow by following the decay process of an injected radioactive tracer. Blood flow patterns are a good indicator of activity levels in different parts of the brain.

Individuals who reported to binge on MDMA did not develop dopamine neurotoxicity. "Using PET methods that bind to brain dopamine and serotonin axon terminals, we found no evidence of dopamine toxicity in abstinent MDMA users, even if they reported prior binge use," McCann said.

"In contrast, as previously, we found significant decreases in brain serotonin markers that were related to extent of prior MDMA use. Further, there was a relationship between brain serotonin markers and memory performance, with increased markers associated with better memory performance."

This study is the first of its kind to establish the relationship between serotonin transporters and cognitive performance. Memory performance in both MDMA users and non-MDMA users was linked with serotonergic binding in brain areas that are typically associated with memory function.

The findings appear to be universal. "This relationship was seen in both MDMA users and controls, suggesting that serotonin systems play a role in short-term memory in healthy individuals and supporting the notion that MDMA-induced serotonin injury plays a role in memory problems that have been found in prior MDMA users," McCann said.

Since the results showed that MDMA users experienced less serotonin transporter binding in multiple brain regions, it was inferred that their impaired performance on memory tasks was related to their serotonergic deficit.

The researchers noted that other factors, such as MDMA-induced sleep deprivation, might have led to poorer cognitive performance. In the meantime, research continues to examine the functional consequences of serotonin, which has been linked to mood, memory and sleep cycles.